Apolipoprotein E (apoE) plays a central role in the metabolism of remnants of triglyceride (TG)-rich particles. ApoE can be separated into 3 major bands (E2, E3, and E4) with each band being inherited in a condominant fashion, the 3 bands being coded by 3 separate alleles at one genetic locus. ApoE2 is the only major band found in most subjects with Type III hyperlipoproteinemia (HLP). In the past year studies have been performed to compare the metabolism of ApoE from a subject homozygous for E2 with apoE from a subject homozygous for E4. In addition, a sensitive double antibody radioimmunoassay for apoE has been developed. ApoE2 was found to have a residence time twice as long as E4 in both normal and Type III HLP subjects and the elevated apoE level found in Type III subjects was shown to be solely due to a catabolic defect of their apoE2. Rat hepatocytes were found to bind apoE4 more avidly than apoE2. These findings are consistent with the hypothesis that the hyperlipidemia found in Type III HLP subjects is due to an abnormal apoE (apoE2) which causes a defective catabolism of remnants of TG-rich particles by the liver.